p-Toluenesulfonic acid → 4-(4-chlorophenyl)-2,3,6,6,9-pentamethyl-6H-thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepine

HRID 1772330Notes

Reaction equation

HRID 1772330 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:9]3[C:24]([CH3:25])=[C:23]([CH3:26])[S:22][C:10]=3[NH:11]/[C:12](=[N:17]\[NH:18][C:19](=O)[CH3:20])/[C:13]([CH3:16])([CH3:15])[N:14]=2)=[CH:4][CH:3]=1.CC1C=CC(S(O)(=O)=O)=CC=1>O1CCCC1>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:9]3[C:24]([CH3:25])=[C:23]([CH3:26])[S:22][C:10]=3[N:11]3[C:19]([CH3:20])=[N:18][N:17]=[C:12]3[C:13]([CH3:16])([CH3:15])[N:14]=2)=[CH:4][CH:3]=1

Participants

4

Reactant 2

HCID 6101p-Toluenesulfonic acidHCID 178475133HCID 178475133, compound

Product 1

HCID 545887644-(4-chlorophenyl)-2,3,6,6,9-pentamethyl-6H-thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepine

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A disposable tube fitted with a septum was charged with (Z)—N′-(5-(4-chlorophenyl)-3,3,6,7-tetramethyl-1H-thieno[2,3-e][1,4]diazepin-2(3H)-ylidene)acetohydrazide (112 mg, 0.288 mmol) and tetrahydrofuran (10 mL). Tosic acid (75 mg, 0.394 mmol, 1.4 equiv) was added, and the solution as stirred at room temperature 30 min, at which point LC/MS analysis indicated complete consumption of the starting material. The solution was concentrated for purification by column chromatography (eluting with dichloromethane/methanol/ammonium hydroxide) to yield an off-white amorphous solid. This solid was further purified by semi-prep HPLC (water/acetonitrile/0.1% trifluoroacetic acid), free-based with a strong cation exchange solid phase extraction column (eluting with ammonia in methanol), and lyophilized to yield 4-(4-chlorophenyl)-2,3,6,6,9-pentamethyl-6H-thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepine as a yellow amorphous solid (m/z=371) (46 mg, 43%). 1H NMR (400 MHz; DMSO): δ 7.48 (s, 4H), 2.60 (s, 3H), 2.39 (s, 3H), 1.97 (s, 3H), 1.57 (s, 3H), 1.07 (s, 3H).

Workup

  1. customA disposable tube fitted with a septum
  2. customconsumption of the starting material
  3. concentrationThe solution was concentrated for purification by column chromatography (eluting with dichloromethane/methanol/ammonium hydroxide)
  4. customto yield an off-white amorphous solid
  5. customThis solid was further purified by semi-prep HPLC (water/acetonitrile/0.1% trifluoroacetic acid), free-based with a strong cation exchange solid phase extraction column (eluting with ammonia in methanol)

Sources & evidence

ORD record
ord-4ff09a0f20fd4f6e9e20098ebf6b80a7
Source dataset
uspto-grants-2016_02
Patent number
US09249161B2

Reaction notes

Loading…